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Prothrombin factor complex

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https://www.readbyqxmd.com/read/28700408/three-versus-four-factor-prothrombin-complex-concentrates-for-factor-based-resuscitation-in-a-porcine-hemorrhagic-shock-model
#1
Donald Michael Moe, Michael Scott Lallemand, John Mason McClellan, Joshua Porter Smith, Shannon T Marko, Matthew J Eckert, Matthew J Martin
BACKGROUND: Bleeding is a leading cause of preventable death following severe injury. Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and reverse oral anticoagulants, but are proposed for use in "factor-based" resuscitation strategies. Few studies exist for this indication in acidosis, or that compare 3-factor (3PCC) versus 4-factor (4PCC) products. We aimed to assess and compare their safety and efficacy in a porcine model of severe hemorrhagic shock and coagulopathy...
July 12, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28698333/research-protocol-for-platelets-in-out-of-hospital-cardiac-arrest-an-observational-case-controlled-feasibility-study-to-assess-coagulation-and-platelet-function-abnormalities-with-rotem-following-out-of-hospital-cardiac-arrest-pohcar
#2
Agnieszka Skorko, Matthew Thomas, Andrew Mumford, Thomas Johnson, Elinor Griffiths, Rosemary Greenwood, Jonathan Benger
INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) has an annual incidence of approximately 60 000 in the UK. Less than 10% of those who receive resuscitation survive to hospital discharge. For OHCA of a presumed cardiac cause, the optimal antiplatelet therapy is currently unknown. Previous studies indicate that a procoagulopathic state exists postcardiac arrest which may contribute to the formation of thrombi and contribute to poor outcomes. However, the administration of antiplatelet therapies needs to be balanced against the increased risk of bleeding that these individuals face...
July 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28691557/emicizumab-prophylaxis-in-hemophilia-a-with-inhibitors
#3
Johannes Oldenburg, Johnny N Mahlangu, Benjamin Kim, Christophe Schmitt, Michael U Callaghan, Guy Young, Elena Santagostino, Rebecca Kruse-Jarres, Claude Negrier, Craig Kessler, Nancy Valente, Elina Asikanius, Gallia G Levy, Jerzy Windyga, Midori Shima
Background Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. Methods We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B)...
July 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28684918/genotype-and-phenotype-correlation-in-intracranial-hemorrhage-in-neonatal-factor-vii-deficiency-among-thai-children
#4
Chanchai Traivaree, Chalinee Monsereenusorn, Arunotai Meekaewkunchorn, Premsak Laoyookhong, Saranya Suwansingh, Boonchai Boonyawat
Congenital factor VII (FVII) deficiency is a rare inherited coagulopathy. The clinical manifestations and clinical findings vary widely, ranging from asymptomatic to life-threatening bleeding, including intracranial hemorrhage (ICH), with prolonged prothrombin time, normal partial thromboplastin time and normal platelet counts, which are confirmed by the low level of FVII assay. Treatment consists of fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), and recombinant activated FVII to treat bleeding and prophylactic therapy...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28684417/noncanonical-proteolytic-activation-of-human-prothrombin-by-subtilisin-from-bacillus-subtilis-may-shift-the-procoagulant-anticoagulant-equilibrium-toward-thrombosis
#5
Giulia Pontarollo, Laura Acquasaliente, Daniele Peterle, Ilaria Artusi, Vincenzo De Filippis
Blood coagulation is a finely regulated physiological process culminating with the factor Xa (FXa)-mediated conversion of the prothrombin (ProT) zymogen to active αthrombin (αT). In the prothrombinase complex on the platelet surface, FXa cleaves ProT at Arg271, generating the inactive precursor prethrombin-2 (Pre2), which is further attacked at Arg320-Ile321 to yield mature αT. Whereas the mechanism of physiological ProT activation has been elucidated in great detail, little is known about the role of bacterial proteases, possibly released in the bloodstream during infection, in inducing blood coagulation by direct proteolytic ProT activation...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28683994/the-effects-of-steroids-on-coagulation-dysfunction-induced-by-cardiopulmonary-bypass-a-steroids-in-cardiac-surgery-sirs-trial-substudy
#6
Domenico Paparella, Alessandro Parolari, Crescenzia Rotunno, Jessica Vincent, Veronica Myasoedova, Pietro Guida, Micaela De Palo, Vito Margari, Philip J Devereaux, Andre Lamy, Francesco Alamanni, Salim Yusuf, Richard Whitlock
Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752)...
April 2017: Seminars in Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28671348/novel-insights-into-the-regulation-of-coagulation-by-factor-v-isoforms-tissue-factor-pathway-inhibitor%C3%AE-and-protein-s
#7
B Dahlbäck
Factor V (FV) is a regulator of both pro- and anticoagulant pathways. It circulates as a single-chain procofactor, which is activated by thrombin or FXa to FVa that serves as cofactor for FXa in prothrombin activation. The cofactor function of FVa is regulated by activated protein C (APC) and protein S. FV can also function as an anticoagulant APC cofactor in the inhibition of FVIIIa in the membrane-bound tenase complex (FIXa/FVIIIa). In recent years, it has become clear that FV also functions in multiple ways in the tissue factor pathway inhibitor (TFPI) anticoagulant pathway...
July 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28660341/low-dose-prothrombin-complex-concentrate-for-warfarin-associated-intracranial-hemorrhage-with-inr-less-than-2-0
#8
Wesley R Zemrak, Kathryn E Smith, Stephen S Rolfe, Teresa May, Robert L Trowbridge, Timothy L Hayes, Gene A Grindlinger, David B Seder
BACKGROUND: Prothrombin complex concentrates (PCCs) have become the first-line therapy for warfarin reversal in the setting of central nervous system (CNS) hemorrhage. Randomized, controlled studies comparing agents for warfarin reversal excluded patients with international normalized ratio (INR) <2, yet INR values of 1.6-1.9 are also associated with poor outcomes. METHODS: We retrospectively reviewed our use of a low-dose (15 units/kg) strategy of 4-factor PCC (4F-PCC) on warfarin reversal (INR 1...
June 28, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28654426/use-of-three-procoagulants-in-improving-bleeding-outcomes-in-the-warfarin-patient-with-intracranial-hemorrhage
#9
Emma P DeLoughery, Thomas G DeLoughery
: When patients on anticoagulation present with intracranial bleeding, stopping the bleeding is paramount. Despite the availability of multiple options to reverse anticoagulation, no study has directly compared the effectiveness of the procoagulants recombinant activated factor VII (rFVIIa), the rFVIIa and 3-factor prothrombin complex concentrate (PCC) combination, and 4-factor PCC on improving patient outcomes compared with a control. This study examined the medical records of 197 warfarin patients with intracranial hemorrhage, an initial international normalized ratio (INR) greater than 1...
June 24, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28635130/prothrombin-complex-concentrate-for-emergent-reversal-of-warfarin-an-international-survey-of-hospital-protocols
#10
J Gorlin, S Kinney, M K Fung, A Tinmouth
For emergent warfarin reversal, four-factor prothrombin complex concentrates (4FPCCs) are recommended by many international guidelines. We surveyed international clinical sites including members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Most sites have emergent warfarin reversal protocols (53% use PCC, 25% use PCC+ plasma and 2% use plasma alone); however, variation between adjusted dosing and fixed dosing was observed.
June 21, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28612131/three-factor-versus-four-factor-prothrombin-complex-concentrate-for-the-emergent-management-of-warfarin-associated-intracranial-hemorrhage
#11
Daniel Fischer, Jeffrey Sorensen, Gabriel V Fontaine
BACKGROUND: Four-factor prothrombin complex concentrates (PCC) produce a more rapid and complete INR correction compared with 3-factor PCC in patients receiving warfarin. It is unknown if this improves clinical outcomes in the setting of intracranial hemorrhage (ICH). METHODS: This multicenter, retrospective cohort study included patients presenting with warfarin-associated ICH reversed with either 4- or 3-factor PCC. The primary outcome was in-hospital mortality...
June 13, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28604569/use-of-four-factor-prothrombin-complex-concentrate-in-the-reversal-of-warfarin-induced-and-nonvitamin-k-antagonist-related-coagulopathy
#12
Hannah Young, Jeremy L Holzmacher, Richard Amdur, Stephen Gondek, Babak Sarani, Mary E Schroeder
: To evaluate the efficacy of international normalized ratio (INR) reversal using four-factor prothrombin complex concentrate (4F-PCC) in nonmedication-induced coagulopathy. We performed a single-site, retrospective cohort study of patients receiving off-label use of 4F-PCC. Cohorts included liver dysfunction if they had acute liver decompensation or cirrhosis without other causative factors of liver failure such as sepsis, coagulopathy of acute sepsis (CAS) if they had documentation of sepsis and no underlying liver disorder, known factor deficiencies, or medication-induced coagulopathy, or warfarin if they were taking warfarin...
June 9, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28583531/does-activated-clotting-time-help-to-predict-innate-coagulopathy-in-end-stage-liver-disease-patients
#13
H-W Jeong, H-M Kwon, K-W Jung, Y-J Moon, I-G Jun, J-G Song, G-S Hwang
BACKGROUND: Measuring activated clotting time (ACT) is widely performed to monitor heparin therapy. Regardless of anticoagulant use, ACT is affected by coagulopathies such as coagulation factor deficiency and thrombocytopenia. However, its use in end-stage liver disease (ESLD) with complex coagulopathy is not well characterized. We evaluated whether ACT could be used to detect innate coagulopathy in ESLD patients. METHODS: We retrospectively assessed Hemochron (International Technidyne, Edison, NJ, USA) ACT (FTCA 510, normal range 105-167 seconds) and INTEM clotting time (CT) of rotational thromboelastometry (ROTEM; ROTEM delta, Pentapharm GmbH, Munich, Germany) (100-240 seconds) in 366 liver transplantation (LT) recipients, simultaneously measured before anesthetic induction for LT...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28543073/rapid-response-to-intravenous-vitamin%C3%A2-k-may-obviate-the-need-to-transfuse-prothrombin-complex-concentrates
#14
Tanmay Sahai, Maria F Tavares, Joseph D Sweeney
BACKGROUND: Patients on warfarin who present with bleeding or who require an urgent procedure are commonly treated with intravenous (IV) vitamin K, which is supplemented with repletion of the vitamin K factors using either plasma or a prothrombin complex concentrate (PCC). In some such cases, use of vitamin K alone could be adequate to achieve acceptable hemostasis. STUDY DESIGN AND METHODS: An algorithm emphasizing the use of vitamin K alone in patients presenting with non-life-threatening bleeding was encouraged, with repeat testing of the international normalized ratio (INR) within 5 hours...
May 19, 2017: Transfusion
https://www.readbyqxmd.com/read/28540468/benefits-and-harms-of-4-factor-prothrombin-complex-concentrate-for-reversal-of-vitamin-k-antagonist-associated-bleeding-a-systematic-review-and-meta-analysis
#15
REVIEW
Marjolein P A Brekelmans, Kim van Ginkel, Joost G Daams, Barbara A Hutten, Saskia Middeldorp, Michiel Coppens
Prothrombin complex concentrate (PCC) is used for reversal of vitamin K antagonists (VKA) in patients with bleeding complications. This study aims to assess benefits and harms of 4-factor PCC compared to fresh frozen plasma (FFP) or no treatment in VKA associated bleeding. PubMed, EMBASE and CENTRAL were searched from 1945 to August 2015. Studies reporting 4-factor PCC use for VKA associated bleeding and providing data on INR normalization, mortality or thromboembolic (TE) complications were eligible. Two authors screened titles and full articles for inclusion, extracted data, and assessed risk of bias...
July 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28537975/reduced-requirement-for-prothrombin-complex-concentrate-for-the-restoration-of-thrombin-generation-in-plasma-from-liver-transplant-recipients
#16
Ezeldeen Abuelkasem, Shaheer Hasan, Michael A Mazzeffi, Raymond M Planinsic, Tetsuro Sakai, Kenichi A Tanaka
BACKGROUND: Plasma transfusion remains the mainstay hemostatic therapy during liver transplantation (LT) in most countries. However, a large volume is required for plasma to achieve clinically relevant factor increases. Prothrombin complex concentrate (PCC) is a low-volume alternative to plasma in warfarin reversal, but its efficacy has not been well studied in LT. METHODS: Blood samples were collected from 28 LT patients at baseline (T0) and 30 minutes after graft reperfusion (T1)...
May 19, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28526142/anticoagulant-reversal-and-anesthetic-considerations
#17
REVIEW
Joseph Meltzer, Joseph R Guenzer
Bleeding complications are a common concern with the use of anticoagulant agents. In many situations, reversing of neutralizing their effects may be warranted. Prothrombin complex concentrate replaces coagulation factors lowered by warfarin, as does fresh frozen plasma, but in a more concentrated form. Protamine negates the effect of heparin and combines chemically with heparin molecules to form an inactive salt. It also partially reverses the effects of low-molecular-weight heparin. Recombinant activated factor VII is a nonspecific procoagulant that activates the extrinsic clotting pathway, resulting in thrombin generation, but does not directly neutralize the activity of any of the new oral anticoagulants...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28512017/a-case-of-autoimmune-severe-acquired-von-willebrand-syndrome-type-3-like
#18
Chakri Gavva, Prapti Patel, Yu-Min Shen, Eugene Frenkel, Ravi Sarode
Von Willebrand disease (VWD) is the most common congenital bleeding disorder and is due to quantitative or qualitative defects of von Willebrand factor (VWF). Acquired defects of VWF, termed acquired von Willebrand syndrome (AVWS), are due to a host of different mechanisms. Autoantibody-mediated AVWS may be associated with lymphoproliferative or immunological disorders, such as systemic lupus erythematosus (SLE). A large majority of AVWS cases are type 1 or type 2A-like and patients tend to have a mild to moderate bleeding tendency...
April 27, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28489305/prolonged-survival-following-pig-to-primate-liver-xenotransplantation-utilizing-exogenous-coagulation-factors-and-costimulation-blockade
#19
J A Shah, M S Patel, N Elias, N Navarro-Alvarez, I Rosales, R A Wilkinson, N J Louras, M Hertl, J A Fishman, R B Colvin, A B Cosimi, J F Markmann, D H Sachs, P A Vagefi
Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in 1968, survival has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous posttransplant infusion of human prothrombin concentrate complex, and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone, and costimulation blockade (belatacept, n = 3 or anti-CD40 mAb, n = 1) to extend survival. Baboon 1 remained well until postoperative day (POD) 25, when euthanasia was required because of cholestasis and plantar ulcers...
August 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28472132/decreased-prothrombin-conversion-and-reduced-thrombin-inactivation-explain-rebalanced-thrombin-generation-in-liver-cirrhosis
#20
Romy M W Kremers, Marie-Claire Kleinegris, Marisa Ninivaggi, Bas de Laat, Hugo Ten Cate, Ger H Koek, Rob J Wagenvoord, H Coenraad Hemker
Impaired coagulation factor synthesis in cirrhosis causes a reduction of most pro- and anticoagulant factors. Cirrhosis patients show no clear bleeding or thrombotic phenotype, although they are at risk for both types of hemostatic event. Thrombin generation (TG) is a global coagulation test and its outcome depends on underlying pro- and anticoagulant processes (prothrombin conversion and thrombin inactivation). We quantified the prothrombin conversion and thrombin inactivation during TG in 30 healthy subjects and 52 Child-Pugh (CP-) A, 15 CP-B and 6 CP-C cirrhosis patients to test the hypothesis that coagulation is rebalanced in liver cirrhosis patients...
2017: PloS One
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